Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20884 | 62875;62876;62877 | chr2:178589075;178589074;178589073 | chr2:179453802;179453801;179453800 |
| N2AB | 19243 | 57952;57953;57954 | chr2:178589075;178589074;178589073 | chr2:179453802;179453801;179453800 |
| N2A | 18316 | 55171;55172;55173 | chr2:178589075;178589074;178589073 | chr2:179453802;179453801;179453800 |
| N2B | 11819 | 35680;35681;35682 | chr2:178589075;178589074;178589073 | chr2:179453802;179453801;179453800 |
| Novex-1 | 11944 | 36055;36056;36057 | chr2:178589075;178589074;178589073 | chr2:179453802;179453801;179453800 |
| Novex-2 | 12011 | 36256;36257;36258 | chr2:178589075;178589074;178589073 | chr2:179453802;179453801;179453800 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/F | rs773806020  |
-1.08 | 0.007 | N | 0.397 | 0.027 | 0.393927044628 | gnomAD-2.1.1 | 1.45E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.14E-05 | 0 |
| C/F | rs773806020 |
-1.08 | 0.007 | N | 0.397 | 0.027 | 0.393927044628 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| C/F | rs773806020 |
-1.08 | 0.007 | N | 0.397 | 0.027 | 0.393927044628 | gnomAD-4.0.0 | 1.15934E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.15479E-05 | 0 | 0 |
| C/R | rs2154183548 |
None | None | N | 0.377 | 0.09 | 0.371344866733 | gnomAD-4.0.0 | 2.74432E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59836E-06 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.1367 | likely_benign | 0.1326 | benign | -1.594 | Destabilizing | None | N | 0.119 | neutral | None | None | None | None | N |
| C/D | 0.2817 | likely_benign | 0.2872 | benign | -0.674 | Destabilizing | 0.004 | N | 0.438 | neutral | None | None | None | None | N |
| C/E | 0.2519 | likely_benign | 0.272 | benign | -0.51 | Destabilizing | 0.001 | N | 0.454 | neutral | None | None | None | None | N |
| C/F | 0.0766 | likely_benign | 0.0712 | benign | -0.954 | Destabilizing | 0.007 | N | 0.397 | neutral | N | 0.465204464 | None | None | N |
| C/G | 0.1138 | likely_benign | 0.0989 | benign | -1.934 | Destabilizing | 0.001 | N | 0.477 | neutral | N | 0.464337673 | None | None | N |
| C/H | 0.0729 | likely_benign | 0.0796 | benign | -2.083 | Highly Destabilizing | None | N | 0.431 | neutral | None | None | None | None | N |
| C/I | 0.1311 | likely_benign | 0.1349 | benign | -0.702 | Destabilizing | 0.001 | N | 0.346 | neutral | None | None | None | None | N |
| C/K | 0.155 | likely_benign | 0.1762 | benign | -0.984 | Destabilizing | None | N | 0.384 | neutral | None | None | None | None | N |
| C/L | 0.1112 | likely_benign | 0.1117 | benign | -0.702 | Destabilizing | None | N | 0.27 | neutral | None | None | None | None | N |
| C/M | 0.1919 | likely_benign | 0.2041 | benign | 0.226 | Stabilizing | 0.041 | N | 0.461 | neutral | None | None | None | None | N |
| C/N | 0.1266 | likely_benign | 0.1254 | benign | -1.258 | Destabilizing | 0.001 | N | 0.441 | neutral | None | None | None | None | N |
| C/P | 0.939 | likely_pathogenic | 0.9341 | pathogenic | -0.973 | Destabilizing | 0.008 | N | 0.411 | neutral | None | None | None | None | N |
| C/Q | 0.1017 | likely_benign | 0.1093 | benign | -0.977 | Destabilizing | 0.002 | N | 0.419 | neutral | None | None | None | None | N |
| C/R | 0.0724 | likely_benign | 0.0761 | benign | -1.104 | Destabilizing | None | N | 0.377 | neutral | N | 0.441671457 | None | None | N |
| C/S | 0.0881 | likely_benign | 0.0846 | benign | -1.698 | Destabilizing | None | N | 0.193 | neutral | N | 0.330844752 | None | None | N |
| C/T | 0.1012 | likely_benign | 0.104 | benign | -1.344 | Destabilizing | None | N | 0.193 | neutral | None | None | None | None | N |
| C/V | 0.1327 | likely_benign | 0.1378 | benign | -0.973 | Destabilizing | None | N | 0.182 | neutral | None | None | None | None | N |
| C/W | 0.183 | likely_benign | 0.1729 | benign | -1.14 | Destabilizing | 0.258 | N | 0.507 | neutral | N | 0.478768407 | None | None | N |
| C/Y | 0.0842 | likely_benign | 0.0806 | benign | -1.031 | Destabilizing | 0.003 | N | 0.42 | neutral | N | 0.465031106 | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.